Early in the epidemic of the Acquired Immunodeficiency Syndrome (AIDS), intravenous drug abusers (IVDA's) were identified as a group at increased risk for disease. This high risk group comprises at a minimum 25% of all domestic cases of AIDS and approximately 34% of cases in New York City. Presently it is estimated that between 25 to 87% of the 200,000 IVDA's in the New York Metropolitan area are infected with HIV. This population is of further importance because it represents a major route of transmission of infection to other adult populations and to children. Nonetheless, insufficient information exists about the epidemiology and natural history of both infection and disease due to HIV among IVDA. We propose to perform a natural history study of HIV seropositive and seronegative IVDA cohorts enrolled in the Montefiore Drug Abuse Treatment Program (DATP). The DATP provides long term methadone maintenance for opiate addiction and is uniquely suited for careful longitudinal studies of IVDA because of high retention rates and close medical monitoring of program patients. This study will be based upon and carry forward the results of a seroprevalence and case control study of 500 enrollees in the DATP which is nearing completion. The prevalence study has provided two large cohorts of IVDA, one seropositive and one seronegative, which will now be followed longitudinally. In addition, to determining the incidence of and natural history of HIV infection in this population, we will seek to identify the variables which may be associated with seroconversion and progression to disease. These will include demographic chacateristics, drug use type, frequency, duration and specific practices, sexual orientation and practices and psychosocial and biologic co-factors. In addition, several hypothesis generated by the prevalence study will be further tested, i.e., importance of cocaine use, needle sharing, etc. Finally, the psychologic and behavioral impact of notification of serologic and disease status will be monitored in a standardized protocol and educational inteventions will be evaluated to determine their effect upon risk reduction. At Montefiore DATP, both HIV seropositive and seronegative participants will be screened prospectively at 6 months intevals. Screening will consist of a detailed standardized interview designed to elicit demographic and drug use variables, complete physical exams, testing for HIV antibodies, and immunologic function and selected HIV cultures. This longitudinal study will be linked to ongoing studies of heterosexual transmission, household transmission and vertical transmission and pregnancy outcome which are supported by the Centers for Disease Control. Data generated from these cohorts will be entered and stored in a fully developed and functioning computerized data management system allowing for sophisticated statistical analysis.